The proposed grant will study the acute and long-term effects of methadone, morphine, cyclazocine and naltrexone on behavior, brain biogenic amine function and pituitaryadrenal responsiveness in stress using experimental animals. The major objective of this study will be to evaluate these effects in view of human drug-assisted treatment models of the narcotic addict. Acute experiments will study the importance of biogenic amine systems and brain area sites to the discriminative stimulus and antinociceptive or antagonistic properties of these drugs. Amine systems will be manipulated by the use of specific chemical agents, by the electrostimulation of specific brain areas, and by the production of specific electrolytic or chemical lesions within specific brain areas. In addition, both methadone and naltrexone will be studied on the developmental behavior of rats. In these studies morphine-induced antinociception and aversion will be studied in rats born to mothers receiving either drug pre- and/or postnatally. BIBLIOGRAPHIC REFERENCES: Rosecrans, J.A., W.T. Chance, and M.D. Schechter: The discriminative stimulus properties of nicotine, d-amphetamine and morphine in dopamine depleted rats. Psychopharm. Comm. 2:346-356 (1976). Hayes, R.L., P.G. Newlon, J.A. Rosecrans and D.J. Maye: Reduction of stimulation-produced analgesia by lysergic acid diethylamide, a depressor of serotonergic neural activity. Brain Res., 1977. In Press.